Bipolar disorder (BD) is a devastating mental disorder characterised by remitting and relapsing episodes of depression and (hypo)mania, which can also include psychotic symptoms such as delusions and hallucinations1. Disease onset is commonly in late adolescence or early adulthood, affecting men and women equally. BD has a lifetime prevalence of 1.0% for bipolar I disorder and 1.1% for bipolar II disorder2. When compared to the general population, BD is a life shortening condition. The higher mortality rates3 are the result of both natural (e.g. cardiovascular disease4,5) and unnatural (e.g. 25%-50% of BD patients will attempt suicide6) causes. BD has a substantial impact on the European Union (EU) population and economy. In 2010, an estimated 3 million people (0.9% of the population) within the EU had been diagnosed with BID7, amounting to a total cost of €21.5 billion, with the majority of costs (€18.0 billion; 83.7%) being indirect such as lost productivity (e.g. sick leave)8.
Diagnosis is still based upon clinical interviews endeavouring to identify BD mood symptoms and patterns. In most cases, the depressive symptoms at the initial presentation of BD overlap with symptoms of major depressive disorder (MDD), whilst manic symptoms overlap with symptoms observed in schizophrenia (SCZ). This overlap of symptoms frequently results in BD being misdiagnosed leading to long delays between the onset of initial symptoms until correct diagnosis. Ghaemi et al. estimated that the average delay for BD patients to be correctly diagnosed was 7.5 years9. Most individuals seek psychiatric care for depressive symptoms at the onset of the disorder10,11, which was shown to correlate with a depressive-predominant polarity12, and 30-69% of these individuals are misdiagnosed13. An MDD misdiagnosis of BD patients is commonly associated with inappropriate antidepressant treatment that can precipitate hypomanic or manic symptoms, worsening the outcome for the patient. Had the individual received a correct diagnosis and been prescribed a mood stabilizer before the use of an antidepressant, their progression into hypomania or mania may have been delayed or even averted.
Despite the established clinical need for an objective test for the diagnosis of BD to be routinely used in conjunction with clinical interviews14,15,16, extensive research into neuroimaging based biomarkers17 and genetic risk factors (e.g. CACNA1C, ODZ4, and NCAN18), has as yet not resulted in a diagnostic test for routine clinical use. A proteomics based approach may prove to be more successful and has already provided promising diagnostic tests for MDD19 and SCZ20.
Therefore, there is a need to develop an objective test, in particular a blood-based molecular biomarker test, for identification of bipolar disorder prior to disease onset, such as prior to the onset of hypomanic or manic symptoms.